Characterization of Identified Dopaminergic Neurons in the Mouse
Olfactory Bulb and Midbrain
Abstract
Dopaminergic (DA) neurons play pivotal roles in diverse brain functions,
spanning movement, reward processing, and sensory perception. DA neurons
are most abundant in the midbrain (Substantia Nigra pars compacta, SNC,
and Ventral Tegmental Area, VTA) and the olfactory bulb (OB) in the
forebrain. Interestingly, a subtype of OB DA neurons is capable of
regenerating throughout life, while a second class is exclusively born
during embryonic development. Emerging evidence in SNC and VTA also
indicates substantial heterogeneity in terms of morphology,
connectivity, and function. To further investigate this heterogeneity
and directly compare form and function of midbrain and forebrain DA
neurons, we performed immunohistochemistry and whole-cell patch-clamp
recordings in ex vivo brain slices from juvenile DAT-tdTomato mice.
After confirming the penetrance and specificity of the dopamine
transporter (DAT) Cre line, we compared soma shape, passive membrane
properties, voltage sags and action potential firing across midbrain and
forebrain DA subtypes. We found that each DA subgroup within midbrain
and forebrain was highly heterogeneous, and that DA neurons across the
two brain areas are also substantially different. These findings
complement previous work in rats as well as gene expression and in vivo
datasets, further questioning the existence of a single “dopaminergic”
neuronal phenotype.